Drug hypersensitivity involves the activation of T cells in an HLA allele–restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell–priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO–specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ–restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO–specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO–induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
Let M be an R-module, where R be a commutative; ring with identity. In this paper, we defined a new kind of submodules, namely T-small quasi-Dedekind module(T-small Q-D-M) and essential T-small quasi-Dedekind module(ET-small Q-D-M). Let T be a proper submodule of an R-module M, M is called an (T-small Q-D-M) if, for all f ∊ End(M), f ≠ 0, implies
This study included nine patients with inactive carrier states of HBV and 14 healthy control groups. The number and the percentage of T-lymphocyte (CD3+ Cells) in the peripheral blood of these groups showed no significant difference. Similar trend was observed when number and percentages of T helper cells (CD4+ cells) and T cytotoxic lymphocytes (CD8+ cells). Moreover, no significant difference in CD4+ /CD8+ cells ratio (P > 0.05) in peripheral blood of patients with inactive carrier state of HBV as compared with healthy control group. The levels of total serum bilirubin (TSB) concentration and alanine aminotransferase (ALT) activity were similar to control group. The levels of immunoglobulin concentration (IgG and IgM) in patients g
... Show MoreA study has been performed to compare the beddings in which ductile iron pipes are buried. In water transmission systems, bends are usually used in the pipes. According to the prescribed layout, at these bends, unbalanced thrust forces are generated that must be confronted to prevent the separation of the bend from the pipe. The bed condition is a critical and important factor in providing the opposite force to the thrust forces in the restraint joint system. Due to the interaction between the native soil and the bedding layers in which the pipe is buried and the different characteristics between them. Also, the interaction with the pipe material makes it difficult to calculate the real forces opposite to the thrust forces and the way they
... Show MoreAbstract That the child is aged 7 years, surrounded by information, knowledge and skillsvaried, which constitute the raw material of experience teaching and is in the rule of inputlearning, if received by the student of these data are positive, these data require research and audit, the style becomes more positive, effective, and then becomes the explorer, butnot done exploration efficiency without the visual, auditory and sensory owned by thechildren. So study aimed to identify the values of the optical track and explore mathematical and find the relationship between them. And use the descriptive approach in a manner the linkon the children of the first year of primary school age (6-7) years in my school Waziriya and Karkh, during the peri
... Show MoreThe aim of this work is to study the effect of mud compositions on it’s rheological behavior under high temperature conditions. Seventeen samples of five types of water base mud in which (fresh water bentonite mud. Lignosulphonate mud, gypsum mud, polymer mud, and salt saturated mud) were tested with different temperatures using the fann viscometer model 50-c. All the tested samples, except the fresh water bentonite mud, have the same trend reduction in both plastic viscosity and yield point with increasing temperature. Six rheological models has been adapted: Bingham plastic, power law, Casson model represent the laboratory data accurately
Each book has a specific style in which its author walks on it from its beginning to its end, and the Holy Qur’an is a book that compiled many methods that were indicative of its miracle, and that it is one unit even though it has been astrologer for twenty-three years.
There is no doubt that knowledge of the Qur’anic methods is one of the pillars of the approach that deals with any of the Qur’an, and the multiplicity of Qur’anic methods is a fact that has many causes. It has been expressed by the Qur’anic discharge and the conjugation of verses to bring them to different methods, and on multiple forms such as nominal, actual, singular Qur’an, presentation, delay, deletion, mention, abbreviation and redundancy. The Qur'ani
The aim of the present investigation was to develop a microsponge delivery system of acyclovir to control its release when applied topically thereby reducing dosing frequency and enhancement patient compliance. The microsponges were produced by the oil in oil emulsion solvent diffusion method. The effect of different formulation and process variables such as internal phase volume, polymer type, drug-polymer ratio, stirring speed and stirring duration on microsponge production yield, loading efficiency, particle size and in-vitro drug release was evaluated. The result showed that the microsponge F2 prepared from Eudrajet RS polymer had optimum physical properties regarding the loading efficiency of 99.71_+ 0.7% and product
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The research aims to reveal the relationship between the use of social networking sites and the image that females make about their physical formation, the nature of the effects, their value judgments about the image of their bodies, their attitudes toward plastic surgery, the most important types of these processes for them, their motivations to conduct them, and the cultural pressures they are exposed to. The study, moreover, investigates in the effects of those plastic surgery on their behavior as active and interacting users with what is published on social media, according to the theory of social comparison. This paper is an attempt to understand the pattern of social networking |
There are many harmful acts that occur from drunkards in this case, especially those resulting from car accidents. The world is witnessing dozens or even hundreds of car accidents due to alcohol consumption. These accidents often result in serious injuries that could lead to the death of the drunk driver and those in the car As well as other persons present in the other vehicles with which the incident occurred or pedestrians on the street, as well as damage to private or public property, and if the order of return of the affected persons on the pretext of civil liability (tort) is made as a direct cause of the harmful act, Is entitled Do they like this refer to the liquor seller or their provider as the culprit? Or are they not related to
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